CA2619426C - Utilisation d'exendines pour le traitement du diabete et la reduction de la masse corporelle - Google Patents
Utilisation d'exendines pour le traitement du diabete et la reduction de la masse corporelle Download PDFInfo
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- CA2619426C CA2619426C CA2619426A CA2619426A CA2619426C CA 2619426 C CA2619426 C CA 2619426C CA 2619426 A CA2619426 A CA 2619426A CA 2619426 A CA2619426 A CA 2619426A CA 2619426 C CA2619426 C CA 2619426C
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- exendin
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Abstract
La présente invention se rapporte à des méthodes permettant de réduire la masse corporelle, de modifier la constitution du corps humain, de traiter le diabète, de réduire HbA1c et de réduire la glycémie quotidienne moyenne, grâce à l'utilisation d'exendines, d'agonistes d'exendines ou d'agonistes d'analogues d'exendines.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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US70960405P | 2005-08-19 | 2005-08-19 | |
US60/709,604 | 2005-08-19 | ||
US77921606P | 2006-03-03 | 2006-03-03 | |
US60/779,216 | 2006-03-03 | ||
PCT/US2006/032354 WO2007024700A2 (fr) | 2005-08-19 | 2006-08-18 | Methodes destinees a traiter le diabete et a reduire la masse corporelle |
Publications (2)
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CA2619426A1 CA2619426A1 (fr) | 2007-03-01 |
CA2619426C true CA2619426C (fr) | 2016-06-21 |
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Application Number | Title | Priority Date | Filing Date |
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CA2619426A Active CA2619426C (fr) | 2005-08-19 | 2006-08-18 | Utilisation d'exendines pour le traitement du diabete et la reduction de la masse corporelle |
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US (7) | US20090239796A1 (fr) |
EP (3) | EP2347762B1 (fr) |
JP (2) | JP5693817B2 (fr) |
KR (1) | KR101059279B1 (fr) |
CN (1) | CN105056211A (fr) |
AU (2) | AU2006283517B2 (fr) |
BR (1) | BRPI0615358B8 (fr) |
CA (1) | CA2619426C (fr) |
CY (1) | CY1122010T1 (fr) |
DK (3) | DK3524261T5 (fr) |
ES (3) | ES2736184T3 (fr) |
FI (1) | FI3524261T3 (fr) |
HR (1) | HRP20150186T1 (fr) |
HU (2) | HUE045165T2 (fr) |
IL (2) | IL189607A (fr) |
LT (2) | LT2347762T (fr) |
MX (1) | MX2008002370A (fr) |
NZ (2) | NZ593461A (fr) |
PL (3) | PL3524261T3 (fr) |
PT (3) | PT3524261T (fr) |
RS (1) | RS53814B1 (fr) |
RU (1) | RU2421237C2 (fr) |
SG (1) | SG184730A1 (fr) |
SI (3) | SI1971362T1 (fr) |
WO (1) | WO2007024700A2 (fr) |
Families Citing this family (97)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
SI2316456T1 (sl) | 2003-04-29 | 2017-10-30 | Orexigen Therapeutics, Inc. | Sestavki za vplivanje na izgubo teže, ki obsegajo opioidni antagonist in bupropion |
WO2006083761A2 (fr) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solutions de solvant/polymere utilisees comme vehicules de suspension |
US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
SI1971362T1 (sl) | 2005-08-19 | 2015-03-31 | Amylin Pharmaceuticals, Llc | Eksendin za zdravljenje diabetesa in zmanjšanje telesne mase |
MX2008014870A (es) | 2006-05-30 | 2009-02-12 | Intarcia Therapeutics Inc | Modulador de flujo para sistema de suministro osmotico con canal interno de dos piezas. |
EP2363112B8 (fr) | 2006-08-09 | 2018-11-21 | Intarcia Therapeutics, Inc. | Système de libération osmotique avec ENSEMBLE DE PISTON |
EP2157967B1 (fr) | 2007-04-23 | 2013-01-16 | Intarcia Therapeutics, Inc | Formulations en suspension de peptides insulinotropes et leurs utilisations |
JP2009019027A (ja) * | 2007-07-16 | 2009-01-29 | Hanmi Pharmaceutical Co Ltd | アミノ末端のアミノ酸が変異したインスリン分泌ペプチド誘導体 |
US8343140B2 (en) | 2008-02-13 | 2013-01-01 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
US20110263496A1 (en) | 2008-05-21 | 2011-10-27 | Amylin Pharmaceuticals, Inc. | Exendins to lower cholesterol and triglycerides |
EP2303025A4 (fr) | 2008-05-30 | 2012-07-04 | Orexigen Therapeutics Inc | Procédés pour traiter des pathologies des graisses viscérales |
EP3685837A1 (fr) | 2008-09-04 | 2020-07-29 | Amylin Pharmaceuticals, LLC | Formulations à libération prolongée à base de supports non aqueux |
HUE037449T2 (hu) | 2008-10-17 | 2018-08-28 | Sanofi Aventis Deutschland | Egy inzulin és egy GLP-1 agonista kombinációja |
WO2010138671A1 (fr) | 2009-05-28 | 2010-12-02 | Amylin Pharmaceuticals, Inc. | Composés agonistes du récepteur glp-1 pour amélioration du sommeil |
CN102770151B (zh) | 2009-08-03 | 2018-07-31 | 因卡伯实验室有限责任公司 | 用于刺激肠道内肠促胰岛素产生的吞咽式囊和方法 |
AU2010298733B2 (en) | 2009-09-28 | 2014-10-09 | Intarcia Therapeutics, Inc. | Rapid establishment and/or termination of substantial steady-state drug delivery |
US20120294855A1 (en) | 2009-11-03 | 2012-11-22 | Eli Lilly & Company | Glp-1 receptor agonist compounds for obstructive sleep apnea |
ES2965209T3 (es) | 2009-11-13 | 2024-04-11 | Sanofi Aventis Deutschland | Composición farmacéutica que comprende desPro36exendina-4(1-39)-Lys6-NH2 y metionina |
EP3831402A1 (fr) | 2009-11-13 | 2021-06-09 | Sanofi-Aventis Deutschland GmbH | Composition pharmaceutique comprenant un agoniste du glp-1, une insuline et de la méthionine |
US8721620B2 (en) | 2009-12-24 | 2014-05-13 | Rani Therapeutics, Llc | Swallowable drug delivery device and methods of drug delivery |
BR112012016783A2 (pt) | 2010-01-11 | 2015-09-01 | Orexigen Therapeutics Inc | "usos do composto de naltrexona ou sal farmaceuticamente aceitável da mesma a bupropiona ou sal farmaceuticamente aceitável da mesma ou de composição dos mesmos e métodos para proporcionar terapia" |
EP2389945A1 (fr) * | 2010-05-28 | 2011-11-30 | Sanofi-Aventis Deutschland GmbH | Composition pharmaceutique comprenant de l'AVE0010 et de l'insuline glargine |
PT2611458T (pt) | 2010-08-30 | 2016-12-16 | Sanofi Aventis Deutschland | Utilização de ave0010 para o fabrico de um medicamento para o tratamento da diabetes mellitus tipo 2 |
WO2012054817A1 (fr) * | 2010-10-22 | 2012-04-26 | Mitokine Bioscience, Llc | Méthode pour retarder l'apparition de l'hyperglycémie et/ou pour traiter l'hyperglycémie, y compris le diabète, avec des acides polyalkylcarboxyliques |
PT2651398T (pt) | 2010-12-16 | 2018-03-09 | Novo Nordisk As | Composições sólidas compreendendo um agonista de glp-1 e um sal de ácido n-(8-(2-hidroxibenzoil)amino) caprílico |
US9629799B2 (en) | 2010-12-23 | 2017-04-25 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9284367B2 (en) | 2010-12-23 | 2016-03-15 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9415004B2 (en) | 2010-12-23 | 2016-08-16 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9402806B2 (en) | 2010-12-23 | 2016-08-02 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8809271B2 (en) | 2010-12-23 | 2014-08-19 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising liraglutide for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9283179B2 (en) | 2010-12-23 | 2016-03-15 | Rani Therapeutics, Llc | GnRH preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US10639272B2 (en) | 2010-12-23 | 2020-05-05 | Rani Therapeutics, Llc | Methods for delivering etanercept preparations into a lumen of the intestinal tract using a swallowable drug delivery device |
US9259386B2 (en) | 2010-12-23 | 2016-02-16 | Rani Therapeutics, Llc | Therapeutic preparation comprising somatostatin or somatostatin analogoue for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US9861683B2 (en) | 2010-12-23 | 2018-01-09 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8980822B2 (en) | 2010-12-23 | 2015-03-17 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising pramlintide for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8734429B2 (en) | 2010-12-23 | 2014-05-27 | Rani Therapeutics, Llc | Device, system and methods for the oral delivery of therapeutic compounds |
US9402807B2 (en) | 2010-12-23 | 2016-08-02 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8809269B2 (en) | 2010-12-23 | 2014-08-19 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising insulin for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8969293B2 (en) | 2010-12-23 | 2015-03-03 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising exenatide for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
US8846040B2 (en) | 2010-12-23 | 2014-09-30 | Rani Therapeutics, Llc | Therapeutic agent preparations comprising etanercept for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
EP2668951B9 (fr) | 2011-01-25 | 2017-03-15 | Viviabiotech, S.L. | Dérivés de 1,2,4-oxadiazol utilisés en tant que médicaments modulateurs du récepteur pour le peptide glp-1 |
US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
EP3225631B1 (fr) | 2011-04-12 | 2019-01-09 | Novo Nordisk A/S | Dérivés glp-1 double-acylates |
US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
WO2013004983A1 (fr) | 2011-07-04 | 2013-01-10 | Imperial Innovations Limited | Nouveaux composés et leurs effets sur le comportement alimentaire |
AR087693A1 (es) | 2011-08-29 | 2014-04-09 | Sanofi Aventis Deutschland | Combinacion farmaceutica para uso en el control glucemico en pacientes con diabetes de tipo 2 |
AR087744A1 (es) | 2011-09-01 | 2014-04-16 | Sanofi Aventis Deutschland | Composicion farmaceutica para uso en el tratamiento de una enfermedad neurodegenerativa |
US10865419B2 (en) * | 2011-10-24 | 2020-12-15 | The Trustees Of The University Of Pennsylvania | Orally administered plastid expressed cholera toxin B subunit-exendin 4 as treatment for type 2 diabetes |
EP2827885B1 (fr) | 2012-03-22 | 2018-08-15 | Novo Nordisk A/S | Compositions de peptides glp-1 et leur préparation |
PT2827845T (pt) | 2012-03-22 | 2019-03-29 | Novo Nordisk As | Composições compreendendo um agente de entrega e sua preparação |
LT3730132T (lt) | 2012-06-06 | 2022-08-25 | Nalpropion Pharmaceuticals Llc | Kompozicija, skirta panaudoti pacientų su didele širdies ir kraujagyslių ligų rizika antsvorio ir nutukimo gydymo būde |
WO2013189988A1 (fr) | 2012-06-20 | 2013-12-27 | Novo Nordisk A/S | Formulation de comprimés comprenant un peptide et un agent d'administration |
UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
PE20151239A1 (es) | 2012-12-21 | 2015-09-08 | Sanofi Sa | Derivados de exendina-4 funcionalizada |
US20160039877A1 (en) | 2013-03-15 | 2016-02-11 | Shenzhen Hightide Biopharmaceutical, Ltd. | Compositions and methods of using islet neogenesis peptides and analogs thereof |
AU2014261336B2 (en) | 2013-05-02 | 2019-02-28 | Novo Nordisk A/S | Oral dosing of GLP-1 compounds |
TW201609795A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 作為雙重glp-1/gip受體促效劑的艾塞那肽-4(exendin-4)胜肽類似物 |
TW201609797A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 雙重glp-1/升糖素受體促效劑 |
EP3080154B1 (fr) | 2013-12-13 | 2018-02-07 | Sanofi | Agonistes doubles du récepteur glp-1/gip |
TW201609796A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 非醯化之艾塞那肽-4(exendin-4)胜肽類似物 |
TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自exendin-4之雙重glp-1/升糖素受體促效劑 |
TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重glp-1/昇糖素受體激動劑之艾塞那肽-4衍生物 |
TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽-4(Exendin-4)之肽類雙重GLP-1/升糖素受體促效劑 |
CN106999553B (zh) * | 2014-05-07 | 2021-11-26 | 诺和诺德股份有限公司 | 使用glp-1和抗-il-21对1型糖尿病的治疗 |
US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
RU2573933C1 (ru) * | 2014-08-21 | 2016-01-27 | Дафот Энтерпрайсис Лимитед | Пептид для лечения сахарного диабета 2-го типа и его осложнений |
US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
CN107106499B (zh) * | 2014-11-02 | 2021-09-17 | 纳诺精密医疗有限公司 | 用于延长释放治疗剂的可植入医药装置 |
DK3229828T5 (da) | 2014-12-12 | 2024-10-14 | Sanofi Aventis Deutschland | Formulering med fast forhold mellem insulin glargin og lixisenatid |
TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患治療 |
TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患之治療 |
BR112017021311A2 (pt) * | 2015-04-07 | 2018-06-26 | Intercept Pharmaceuticals Inc | composições farmacêuticas para terapia de combinação |
ES2887723T3 (es) | 2015-05-22 | 2021-12-27 | Univ Leland Stanford Junior | Tratamiento de hipoglucemia posbariátrica con exendina(9-39) |
KR101661332B1 (ko) * | 2015-05-28 | 2016-09-29 | (의료)길의료재단 | 글루카곤 유사 펩타이드-1 수용체 항진제를 포함하는 근감소증 치료용 약학 조성물 |
EP3302354B1 (fr) | 2015-06-03 | 2023-10-04 | i2o Therapeutics, Inc. | Systèmes de mise en place d'implant |
AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
AR105284A1 (es) | 2015-07-10 | 2017-09-20 | Sanofi Sa | Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón |
US20170098040A1 (en) * | 2015-10-06 | 2017-04-06 | Scale Down | Weight management system and method |
WO2017152014A1 (fr) | 2016-03-04 | 2017-09-08 | Eiger Biopharmaceuticals, Inc. | Traitement de l'hypoglycémie hyperinsulinémique avec des dérivés de l'exendine-4 |
WO2017181007A1 (fr) * | 2016-04-15 | 2017-10-19 | Robert Doyle | Amélioration d'un médicament peptidique utilisant des conjugués de vitamine b12 et d'un substrat de liaison de l'haptocorrine |
RU2760007C2 (ru) | 2016-05-16 | 2021-11-22 | Интарсия Терапьютикс, Инк. | Полипептиды, селективные к рецепторам глюкагона, и способы их применения |
USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
EP3515408A1 (fr) | 2016-09-23 | 2019-07-31 | Delpor, Inc. | Compositions stables pour composés mimétiques de l'incrétine |
JP2019535734A (ja) | 2016-11-21 | 2019-12-12 | アイガー・バイオファーマシューティカルズ・インコーポレイテッドEiger Biopharmaceuticals, Inc. | エキセンディン(9−39)の緩衝製剤 |
IL307966A (en) | 2017-01-03 | 2023-12-01 | Intarcia Therapeutics Inc | Methods involving continuous administration of a GLP-1 receptor agonist and co-administration of a drug |
WO2018136505A1 (fr) * | 2017-01-17 | 2018-07-26 | Wayne State University | Compositions de polymère zwitterionique-insuline et procédés associés |
MX2019010651A (es) | 2017-03-08 | 2020-01-13 | Intarcia Therapeutics Inc | Aparato y métodos para administración de un compuesto nauseogénico desde un dispositivo de administración de fármacos. |
US11795201B2 (en) | 2017-04-14 | 2023-10-24 | University Of Massachusetts | Brown fat-selective adipokines |
WO2018205233A1 (fr) | 2017-05-11 | 2018-11-15 | 深圳君圣泰生物技术有限公司 | Utilisation d'un composé polypeptidique dans le traitement de la pancréatite aiguë |
SG11202006595RA (en) | 2018-02-02 | 2020-08-28 | Novo Nordisk As | Solid compositions comprising a glp-1 agonist, a salt of n-(8-(2-hydroxybenzoyl)amino)caprylic acid and a lubricant |
WO2019240755A1 (fr) * | 2018-06-11 | 2019-12-19 | Wellesley Pharmaceuticals, Llc | Compositions pharmaceutiques et procédés pour une perte pondérale |
KR20210077693A (ko) * | 2018-10-12 | 2021-06-25 | 미라키 이노베이션 씽크 탱크 엘엘씨 | 지방 감소용 냉각 용액 |
KR20210081376A (ko) * | 2018-10-30 | 2021-07-01 | 지아닝 리우 | Glp-1 수용체 작용제 활성을 갖는 glp-1 폴리펩티드 및 그의 용도 |
CA3180674A1 (fr) | 2020-04-22 | 2021-10-28 | Bayer Aktiengesellschaft | Combinaison de finerenone et d'un inhibiteur de sglt2 pour le traitement et/ou la prevention de maladies cardiovasculaires et/ou renales |
KR102556528B1 (ko) * | 2020-12-08 | 2023-07-17 | 경희대학교 산학협력단 | 대사성 질환 예방, 개선 또는 치료용 조성물 |
Family Cites Families (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US386998A (en) | 1888-07-31 | Boiler | ||
US3490597A (en) | 1966-07-22 | 1970-01-20 | Purolator Products Inc | Cover plate for spin-on-filter |
ATE135370T1 (de) | 1988-12-22 | 1996-03-15 | Kirin Amgen Inc | Chemisch modifizierte granulocytenkolonie erregender faktor |
US5445781A (en) | 1991-08-28 | 1995-08-29 | Centro Sviluppo Settori Impiego S.R.L. | Process for the injection molding of non-precatalyzed polymerizable resins at high-pressure and flow |
US5509305A (en) | 1992-02-12 | 1996-04-23 | Daniel Industries, Inc. | Closely coupled, dual turbine volumetric flow meter |
US5656297A (en) | 1992-03-12 | 1997-08-12 | Alkermes Controlled Therapeutics, Incorporated | Modulated release from biocompatible polymers |
US6284727B1 (en) | 1993-04-07 | 2001-09-04 | Scios, Inc. | Prolonged delivery of peptides |
US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
GB2282891B (en) | 1993-10-13 | 1997-09-03 | Tokai Rika Co Ltd | Acceleration detecting apparatus |
US5650173A (en) | 1993-11-19 | 1997-07-22 | Alkermes Controlled Therapeutics Inc. Ii | Preparation of biodegradable microparticles containing a biologically active agent |
EP0998917A1 (fr) | 1993-11-19 | 2000-05-10 | Alkermes Controlled Therapeutics Inc. II | Préparastion de microparticules biodégradables contentant un agent biologiquement actif |
US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
ES2359031T3 (es) | 1996-08-08 | 2011-05-17 | Amylin Pharmaceuticals, Inc. | Composición farmacéutica que comprende un péptido de exendina-4. |
ATE304864T1 (de) | 1997-01-07 | 2005-10-15 | Amylin Pharmaceuticals Inc | Verwendung von exedinen und deren antagonisten zur verminderung der lebensmittelaufnahme |
EP1512395A1 (fr) | 1997-07-18 | 2005-03-09 | Azopax Therapeutics LLC | Macromères biodégradables permettant de libérer de manière régulée des substances biologiquement actives |
DE122007000001I1 (de) | 1999-01-14 | 2007-06-28 | Amylin Pharmaceuticals Inc | Neue exendin agonist Formulierungen und deren Verabreichung |
AU770712B2 (en) | 1999-01-14 | 2004-02-26 | Amylin Pharmaceuticals, Inc. | Methods for glucagon suppression |
US20030087820A1 (en) * | 1999-01-14 | 2003-05-08 | Young Andrew A. | Novel exendin agonist formulations and methods of administration thereof |
US6924264B1 (en) | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
CA2372214A1 (fr) * | 1999-04-30 | 2000-11-09 | Amylin Pharmaceuticals, Inc. | Exendines modifiees et agonistes de l'exendine |
US6162260A (en) | 1999-05-24 | 2000-12-19 | Novo Nordisk Biochem North America, Inc. | Single-bath biopreparation and dyeing of textiles |
WO2001051078A1 (fr) | 2000-01-10 | 2001-07-19 | Amylin Pharmaceuticals, Inc. | Utilisation d'exendines et d'agonistes de ces dernieres pour moduler les taux de triglycerides et pour traiter la dyslipidemie |
US6602997B2 (en) | 2000-04-27 | 2003-08-05 | Shin-Etsu Bio, Inc. | Whole cell and cell-debris polysaccharide |
US6495164B1 (en) | 2000-05-25 | 2002-12-17 | Alkermes Controlled Therapeutics, Inc. I | Preparation of injectable suspensions having improved injectability |
US6479065B2 (en) | 2000-08-10 | 2002-11-12 | Alkermes Controlled Therapeutics, Inc. | Process for the preparation of polymer-based sustained release compositions |
US6824822B2 (en) | 2001-08-31 | 2004-11-30 | Alkermes Controlled Therapeutics Inc. Ii | Residual solvent extraction method and microparticles produced thereby |
AU3938402A (en) | 2000-12-13 | 2002-06-24 | Lilly Co Eli | Chronic treatment regimen using glucagon-like insulinotropic peptides |
US6819912B2 (en) | 2001-11-05 | 2004-11-16 | Freescale Semiconductor, Inc. | Variable frequency switching amplifier and method therefor |
US7092459B2 (en) | 2001-11-08 | 2006-08-15 | Qualcomm, Incorporated | Frequency tracking using pilot and non-pilot symbols |
GB0206792D0 (en) | 2002-03-22 | 2002-05-01 | Leuven K U Res & Dev | Normoglycemia |
US20040121009A1 (en) | 2002-10-17 | 2004-06-24 | Alkermes Controlled Therapeutics, Inc. | Method of modifying the release profile of sustained release compositions |
AU2003286472A1 (en) | 2002-10-17 | 2004-05-04 | Alkermes Controlled Therapeutics, Inc. Ii | Microencapsulation and sustained release of biologically active polypeptides |
US7790681B2 (en) | 2002-12-17 | 2010-09-07 | Amylin Pharmaceuticals, Inc. | Treatment of cardiac arrhythmias with GLP-1 receptor ligands |
WO2005041873A2 (fr) * | 2003-10-24 | 2005-05-12 | Azopax Therapeutics Llc | Formulation de l'exendine-4 |
WO2005040195A2 (fr) | 2003-10-24 | 2005-05-06 | Azopax Therapeutics Llc | Formulation d'exendines |
TWI353250B (en) | 2003-12-16 | 2011-12-01 | Ipsen Pharma Sas | Glp-1 pharmaceutical compositions |
KR101040415B1 (ko) | 2004-04-15 | 2011-06-09 | 알케르메스,인코포레이티드 | 중합체 기재 지속적 방출 방법 |
US7456254B2 (en) * | 2004-04-15 | 2008-11-25 | Alkermes, Inc. | Polymer-based sustained release device |
US8273794B2 (en) | 2004-05-14 | 2012-09-25 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
CA2566354C (fr) | 2004-05-28 | 2016-01-12 | Oryxe | Melange pour administration transdermique de composes a poids moleculaire faible et eleve |
KR101231856B1 (ko) | 2004-08-12 | 2013-02-08 | 큐피에스 엘엘씨 | 생물학적 활성 화합물의 제어 방출 전달용 약학 조성물 |
US20060034889A1 (en) | 2004-08-16 | 2006-02-16 | Macromed, Inc. | Biodegradable diblock copolymers having reverse thermal gelation properties and methods of use thereof |
US7442682B2 (en) | 2004-10-19 | 2008-10-28 | Nitto Denko Corporation | Transepithelial delivery of peptides with incretin hormone activities |
US8389472B2 (en) | 2005-08-19 | 2013-03-05 | Amylin Pharmaceuticals, Llc | Exendin-4 to treat nonalcoholic steatohepatitis and nonalcoholic fatty liver disease |
SI1971362T1 (sl) | 2005-08-19 | 2015-03-31 | Amylin Pharmaceuticals, Llc | Eksendin za zdravljenje diabetesa in zmanjšanje telesne mase |
US7512298B2 (en) | 2006-12-01 | 2009-03-31 | 3M Innovative Properties Company | Optical sensing methods |
IT1402944B1 (it) | 2010-12-15 | 2013-09-27 | Sarong Spa | Capsula per bevande e relativa macchina per utilizzare detta capsula |
US11638099B2 (en) | 2011-12-23 | 2023-04-25 | Shenzhen Shokz Co., Ltd. | Bone conduction speaker and compound vibration device thereof |
JP6226510B2 (ja) | 2012-01-27 | 2017-11-08 | キヤノン株式会社 | 画像処理システム、処理方法及びプログラム |
ITMI20130325A1 (it) | 2013-03-05 | 2014-09-06 | Telecom Italia Spa | Metodo per misurare e monitorare il livello di accesso a dati personali generati da risorse di un dispositivo d'utente |
US9816387B2 (en) | 2014-09-09 | 2017-11-14 | United Technologies Corporation | Attachment faces for clamped turbine stator of a gas turbine engine |
CA2914090C (fr) | 2015-03-31 | 2023-08-01 | Allen-Vanguard Corporation | Recepteur de diffusion en continu du domaine temporel et du domaine de frequence |
US9714199B2 (en) | 2015-09-17 | 2017-07-25 | I P Creations Limited | Concealed amalgamated explosive neutralizer and method of manufacture |
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